Although it has traditionally been assumed that the CNS and the immune system are separate and independent, recent evidence increasingly suggests that these systems are interrelated. One line of evidence is based upon a few reports of behavioral conditioning of immunological responses, particularly immunosuppression. Since these reports have been largely demonstrational in nature, the question of generality remains unanswered. In the present proposal conditioned immunosuppression will be studied in a wide range of conditioning preparations, some of which involve complex associations. Immunological responses will be assessed with techniques which measure changes at the cellular rather than the serum level. Together, these procedures will enable us to correlate precisely the degree to which these systems chance together as a function of various independent variables. Mice will be exposed to Pavlovian conditioning procedures in which gustatory, olfactory, and exteroceptive conditioned stimuli (CS) are paired with an unconditioned stimulus (US), cyclophosphamide, which has immunosuppressive effects. Conditioned immunosuppression will be examined as a function of CS- and/or US-magnitude, CS-US delay, and in terms of resistance to experimental extinction. In other experiments, potentiation of conditioned immunosuppression will be examined in a compound stimulus preparation. In still others, external stimulus control of immunosuppression will be explored in a context-conditioning paradigm. In a final experiment, conditioned immunoenhancement will be attempted by employing an antigen as the US. These experiments have important theoretical implications, not only in terms of advancing our understanding of the immune system and its susceptibility to modulation by external factors, but also in terms of furthering our knowledge of the types of response systems which are subject to control by Pavlovian processes. They also have long range implications for treatment of a variety of neoplastic and immunologic diseases as well as internally- and externally-produced stress.